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Adriamycin‐induced nephropathy in rats: Functional and cellular effects characterized by MRI
Author(s) -
Egger Christine,
Cannet Catherine,
Gérard Christelle,
Debon Corinne,
Stohler Nadine,
Dunbar Andrew,
Tigani Bruno,
Li Jianping,
Beckmann Nicolau
Publication year - 2015
Publication title -
journal of magnetic resonance imaging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.563
H-Index - 160
eISSN - 1522-2586
pISSN - 1053-1807
DOI - 10.1002/jmri.24603
Subject(s) - medicine , nephropathy , perfusion , fibrosis , magnetic resonance imaging , cd68 , renal function , pathology , kidney , histology , kidney disease , bolus (digestion) , infiltration (hvac) , cellular infiltration , urology , immunohistochemistry , endocrinology , radiology , inflammation , physics , diabetes mellitus , thermodynamics
Purpose To assess with magnetic resonance imaging (MRI) adriamycin‐induced nephropathy in living rats, an established model for proteinuric renal disease was used. Materials and Methods Functional information of contrast agent clearance was obtained with dynamic contrast‐enhanced (DCE) imaging following intravenous Gd‐DOTA administration. Perfusion data were obtained with a bolus tracking technique comprising intravenous injection of superparamagnetic iron oxide (SPIO) nanoparticles. Cellular information was derived from anatomical images acquired 24 hours after SPIO. Treatment with the transforming growth factor‐β 123 (TGF‐β 1,2,3 ) antibody, 1D11, started 1 week after adriamycin. Histology was performed at week 6 post‐adriamycin. Results Tracer washout rates derived by DCE‐MRI decreased by 65.5% with respect to baseline at week 6 post‐adriamycin. The impaired kidney function agreed with glomerulopathy, nephropathy and fibrosis revealed histologically (picrosirius collagen staining in adriamycin‐treated rats increased by 125.8% [ P = 0.005] with respect to controls). Perfusion was reduced by 16.1%. Images acquired 24 hours after SPIO presented contrast changes that correlated inversely with the histologically determined iron content (R = −0.74, P = 2.6 × 10 −4 ). In adriamycin‐challenged animals, iron was found in macrophages and in sclerotic tubuli, only in areas where macrophages were present. Treatment with 1D11 did not improve the adriamycin‐induced renal injury. Conclusion MRI provides longitudinal functional and cellular (macrophage infiltration) information that correlates with nephropathy development in adriamycin‐challenged rats. J. Magn. Reson. Imaging 2014 . © 2014 Wiley Periodicals, Inc . J. Magn. Reson. Imaging 2015;41:829–840. © 2014 Wiley Periodicals, Inc.